Kaempferol inhibits VEGF expression and in vitro angiogenesis through a novel ERK-NFκB-cMyc-p21 pathway

Kaempferol has been reported to reduce the risk of ovarian cancer, but the mechanism is not completely understood. In this study, we tend to expand our understanding on how kaempferol regulates VEGF expression and angiogenesis in ovarian cancer cells. We timed VEGF secretion, and studied in vitro angiogenesis by kaempferol treatment. Gene expression was examined by qRT-PCR, ELISA, western blotting, or luciferase assay, and pathways were examined by manipulating genetic components with plasmid or siRNA transfection. It was found that kaempferol time-dependently inhibited VEGF secretion, and suppressed in vitro angiogenesis. Kaempferol down-regulated ERK phosphorelation as well as NF kappa B and cMyc expression, but promoted p21 expression. Examination of relationship between these genes suggested a novel ERK-NF kappa B-cMyc-p21-VEGF pathway, which accounts for kaempferol's angioprevention effects in ovarian cancer cells. This data supplements our comprehension of the mechanisms behind kaempferol's biological influence in ovarian cancer cells, and better characterised kaempferol toward chemoprevention. (C) 2011 Elsevier Ltd. All rights reserved.